N-[2-[(S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide commonly known as Apremilast is a phosphodiesterase 4 (PDE4) inhibitor. Apremilast was approved by the USFDA for the treatment of adults with active psoriatic arthritis.
U.S. Pat. No. 7,427,638B2 specifically describes Apremilast, its related compounds and process for their preparation.
U.S. Pat. No. 7,893,101B2 describes seven crystalline polymorphic forms of Apremilast namely form-A, form-B, form-C, form-D, form-E, form-F and form-G and also described process for their preparation.
U.S. Pat. No. 7,893,101B2 patent also describes mixture of crystalline form-A, form-B, form-C, form-D, form-E, form-F, form-G of Apremilast with amorphous form.
Since the development of new polymorphic forms of an active pharmaceutical ingredient provides new opportunity to improve the performance characteristics of pharmaceutical finished product, the development of new polymorphic forms is always encouraged.
Furthermore, solid state study of an active pharmaceutical ingredient aims to widen the variety of crystalline forms that a formulation scientist has available for designing a pharmaceutical dosage form with desired characteristics.
The present inventors surprisingly found novel crystalline polymorph of N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide having advantageous properties which is useful and well suitable for the preparation of various pharmaceutical compositions.
The present inventors also developed improved process for the preparation of N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)-2-(met)ethyl]-2,3-dihydro-1,3-dioxo-H-isoindol-4-yl]acetamide compound of formula-1 and intermediates thereof.